Interleukin-10 inducing activity of LK423, a phthalimido-desmuramyldipeptide compound

A new phthalimido compound, N-[2-(2-phthalimidoethoxy)acetyl]-L-alanyl-D-glutamic acid (CAS 142489-47-2, LK423), was examined along with other N-acyl-desmuramyldipeptide compounds for possible immunomodulating activities in cyclophosphamide (Cy)-treated mice. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Northern blot assays demonstrated that multiple subcutaneous injections of LK423 (1 to 50 micrograms/days, for 4 days) into these mice resulted in upregulating interleukin-10 (IL-10) gene expression in the spleen. In contrast to IL-10, expression of interferon-gamma (IFN-gamma) gene was reduced by treating with this compound. The culture supernatant of spleen cells obtained from the mice that had received LK423 injections was found to contain a larger amount of IL-10 protein than in the culture supernatant of the spleen obtained from the mice that received no LK423 injections when tested by enzyme-linked immunosorbent assay (ELISA). Conversely to IL-10, the concentration of IFN-gamma was lower in the culture supernatant from the LK423-treated group than that in the control group. In contrast to this compound, other N-acyl-desmuramyldipeptide derivatives carrying a L-alanyl-D-isoglutamine moiety, and other immunological stimulants showed an activity to augment production of IFN-gamma and reduce the gene expression of IL-10. The immunological activities of this new phthalimido desmuramyldipeptide compound, LK423, are discussed from the point of view of its therapeutic application.